| First Author | Nakamura M | Year | 2003 |
| Journal | Endocrinology | Volume | 144 |
| Issue | 12 | Pages | 5441-9 |
| PubMed ID | 14500574 | Mgi Jnum | J:87245 |
| Mgi Id | MGI:2683963 | Doi | 10.1210/en.2003-0717 |
| Citation | Nakamura M, et al. (2003) Osteoprotegerin regulates bone formation through a coupling mechanism with bone resorption. Endocrinology 144(12):5441-9 |
| abstractText | Deficiency of osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of nuclear factor-kappaB ligand (RANKL), in mice induces osteoporosis caused by enhanced bone resorption, but also accelerates bone formation. We examined whether bone formation is coupled with bone resorption in OPG-deficient (OPG-/-) mice using risedronate, an inhibitor of bone resorption. Histomorphometric analysis showed that bone formation-related parameters (e.g. mineral apposition rate and osteoblast surface/bone surface) in OPG-/- mice sharply decreased with suppression of bone resorption by daily injection of risedronate for 30 d. OPG-/- mice exhibited high serum alkaline phosphatase activity and osteocalcin concentration, both of which were decreased to the levels in wild-type mice by the risedronate injection. Serum levels of RANKL were markedly elevated in OPG-/- mice, but were unaffected by risedronate. The ectopic bone formation induced by bone morphogenetic protein-2 implantation into OPG-/- mice was not accelerated even with a high turnover rate of bone, but attenuation of mineral density from the ectopic bone was more pronounced than that in wild-type mice. These results suggest that bone formation is coupled with bone resorption at local sites in OPG-/- mice, and that serum RANKL levels do not reflect this coupling. |
